Disease Activity Indices in Rheumatoid Arthritis: Comparative Performance to Detect Changes in Function, IL-6 Levels, and Radiographic Progression.

Sebastián C Rodriguez-García,Nuria Montes,Loreto Carmona,Luis Rodriguez-Rodriguez,Isabel Castrejón,José Ivorra-Cortes,Ana Triguero-Martinez,Isidoro González-Álvaro

doi:10.3389/fmed.2021.669688

Abstract

Objective: To compare the capacity of various disease activity indices to evaluate changes in function, IL-6 levels, and radiographic progression in early and established rheumatoid arthritis (RA).Methods: Secondary data analysis of a clinical trial assessing the efficacy of tocilizumab in patients with established RA (ACT-RAY) and a longitudinal prospective register of early arthritis (PEARL). Targeted outcomes were changes in physical function, measured with the health assessment questionnaire (HAQ), IL-6 serum levels, and radiographic progression. The “Hospital Universitario La Princesa Index” (HUPI), DAS28 using erythrocyte sedimentation rate and SDAI were the disease activity indices compared. Models adjusted for age and sex were fitted for each outcome and index and ranked based on the R2 parameter and the quasi-likelihood under the independence model criterion.Results: Data from 8,090 visits (550 patients) from ACT-RAY and 775 visits (534 patients) from PEARL were analyzed. The best performing models for HAQ were the HUPI (R2 = 0.351) and SDAI ones (R2 = 0.329). For serum IL-6 levels, the SDAI (R2 = 0.208) followed by the HUPI model (R2 = 0.205). For radiographic progression in ACT-RAY, the HUPI (R2 = 0.034) and the DAS28 models (R2 = 0.026) performed best whereas the DAS28 (R2 = 0.030) and HUPI models (R2 = 0.023) did so in PEARL.Conclusions: HUPI outperformed other indices identifying changes in HAQ and radiographic progression and performed similarly to SDAI for IL-6 serum levels.

Highlights

Routine management of rheumatoid arthritis (RA) using the treat-to-target [1] and tight-control [2] strategies require validated tools to measure disease activity
Data from the variables age, Hospital Universitario La Princesa Index” (HUPI), disease activity score of 28 joints (DAS28), and simplified disease activity index (SDAI) were scaled and centered. β, β-coefficients; SE, Standard Error; quasi-likelihood under the independence model criterion (QIC), quasi-likelihood under the Independence model criterion; health assessment questionnaire (HAQ), Health Assessment Questionnaire; HUPI, Hospital Universitario La Princesa Index; DAS28, Disease Activity Score of 28 joints; SDAI, Simplified Disease Activity Index. *This model was developed with data from ACT-RAY (541 patients and 6778 visits) and validated in prospective register of early arthritis (PEARL). (532 patients and 2032 visits)
Data from the variables HUPI, DAS28, and SDAI were scaled and centered. β, βcoefficients; SE, Standard Error; QIC, quasi-likelihood under the Independence model criterion; IL-6, Interleukin-6; HUPI, Hospital Universitario La Princesa Index; DAS28, Disease Activity Score of 28 joints; SDAI, Simplified Disease Activity Index. *This model was developed with 80% of data from PEARL (201 patients and 543 visits) and validated in the remaining 20%. (111 patients and 141 visits)

Summary

Introduction

Routine management of rheumatoid arthritis (RA) using the treat-to-target [1] and tight-control [2] strategies require validated tools to measure disease activity. Different cohorts have shown that DAS28 and SDAI may be sex-biased, as they include a pain rating and erythrosedimentation rate (ESR), both usually higher in women This potential bias could lead rheumatologists to over-treat women with RA [6, 7]. HUPI includes the same variables as DAS28 but its calculation can be done either with ESR, C-Reactive Protein (CRP), or both, depending on their availability, as a way to tackle missing data [8] This index developed and validated in an early arthritis cohort [8], has disease activity cut-offs with higher areas under the curve in comparison to DAS28, SDAI, and CDAI [9]. Based on its psychometric properties, the 2019 update of the American College of Rheumatology recommended RA disease activity measures included HUPI among the indices that fulfil minimum standards for regular use in most clinical settings [11]

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Conclusion